Anti-atherogenic Effects of 17 beta-Estradiol
Patti, A. M.
Isenović, Esma R.
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Estrogens are secreted primarily by the ovaries and placenta, by the testes in men and also produced by peripheral steroidogenic conversion. The 3 major naturally occurring estrogens are: 17 beta-estradiol (E-2), estrone and estriol, of which E-2 is the predominant and most active. The actions of E-2 are mediated by at least 3 different receptors - the classical ERs (ER alpha and ER beta) and G-protein coupled receptor 30 (GPR30). E-2 signaling in cardiomyocytes involves ER alpha- and ER beta-independent pathways, and treatment with the E-2 receptor antagonists (Selective Estrogen Receptor Modulators- SERMs), which are agonists of GPR30, inhibits cardiac cell growth. Effects of E-2 in preventing endothelial dysfunction, a prerequisite of atherosclerosis, are well recognized. Atherosclerosis involves interaction between the cells of the arterial wall endothelial cells (EC) and vascular smooth muscle cell (VSMC), as well as migration of macrophages into wall tunica media. It is predomina...ntly developed at sites with abnormally high shear stress, such as bifurcations or branching of arteries, initiated by an injury to the endothelium and exposure to atherogenic lipids and toxins, such as those contained in tobacco smoke or infectious agents. Animal studies have shown effects of E-2 in preventing atherosclerosis, inflammation and endothelial or vascular dysfunction. Gender differences along this pathogenic pathway have been also described. We review the data from the available animal and human studies, which focus on anti-atherogenic effects of E-2. These studies represent evidence, albeit indirect, for an inhibitory effect of E-2 on the progression of coronary artery atherosclerosis.